Krabbe Disease

Researchers are evaluating a gene therapy called AAV9-GLB1 for treating Type I and Type II GM1 gangliosidosis, a rare and fatal disorder that destroys nerve cells due to a deficiency in the enzyme beta-galactosidase. This trial aims to test if the gene therapy can help improve symptoms related to these types of GM1 gangliosidosis. The study is a Phase 1/2 non-randomized trial focusing on safety and effectiveness in children ranging from 6 months to 12 years old, sponsored by the National Human Genome Research Institute (NHGRI). Participants will receive a single intravenous infusion of the AAV9-GLB1 gene therapy at doses determined in stages. In Stage 1, different groups of Type I and Type II subjects will receive varying doses to assess safety. Immune system modulation drugs such as rituximab, sirolimus, methylprednisolone, and prednisone will be given before and after gene therapy to reduce immune reactions. Participants will stay at the study site for 8 to 10 weeks initially and may remain for additional safety monitoring after infusion. Stage 2 will administer the dose selected based on Stage 1 data, with further assessments planned. During the study, participants will undergo many tests including blood and urine tests, heart and hearing assessments, ultrasounds, EEGs, lumbar punctures, MRIs, bone scans, IQ and speech tests, and neurological exams. Central line placement and skin biopsies may also be done. Follow-up visits will occur at 3 and 6 months after treatment, then every 6 months for 2 years, and again at 3 years, with yearly visits for 2 more years in an extension study. Researchers will monitor safety, brain development, neurological function, motor skills, and immune responses throughout the study period.

Researchers are conducting a study to systematically screen newborns in the Normandy region for lysosomal storage diseases such as Mucopolysaccharidosis type I and Pompe disease. This observational study aims to evaluate the occurrence and epidemiology of these diseases using dried blood samples collected from newborns. The study is based on previous pilot work and seeks to include about 100,000 newborns over a period of three years. All newborns born in Normandy maternity hospitals who are participating in the national neonatal screening program will have additional blood samples collected on blotting paper for this study. The screening occurs within the first few days after birth, typically from day 2 to day 4. The study will continue until the target number of participants is reached. Participants will have blood samples collected as part of routine neonatal screening, with extra samples taken specifically for this research. The main outcome measured is the number of newborns screened relative to the number of samples collected. Secondary outcomes include the number of positive cases detected for Mucopolysaccharidosis type I and Pompe disease. The study involves parental consent and monitors newborns during these early days, with no further intervention or long-term follow-up described.

Researchers at the University of Texas Health Science Center at San Antonio are studying individuals with chromosome 18 abnormalities to better understand the genetic causes and effects of these conditions. The study aims to identify how growth hormone deficiency and other genetic factors impact brain structure and cognitive function, as well as physical and behavioral traits. The goal is to provide comprehensive medical and educational resources, perform clinical and basic research, and develop treatments to improve the lives of affected individuals. Participants undergo various evaluations including genetic testing of DNA from subjects and their parents to determine genotype. Clinical assessments include testing growth hormone and other hormone levels, psychiatric and neuropsychological evaluations, audiology and ENT exams, brain MRI scans, genetic dysmorphology, neurology, dental, speech pathology, gastrointestinal, orthopedic, and ophthalmologic examinations. These assessments are longitudinal, with participants of a wide age range, and not all tests apply to every participant at every visit. Participants will be involved in thorough clinical evaluations and multiple specialized exams over time to gather detailed health data. These include hormone tests, brain imaging, behavioral and cognitive assessments, and physical exams. Researchers will monitor growth hormone status and other health markers to understand the condition's impact. The study is ongoing and designed to provide long-term data to guide future treatments and support. Total participation time varies depending on individual assessments and follow-up needs.

Researchers are collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation (HSCT) using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants: umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physician's guidance at the UPMC Children's Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease (GVHD) and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients' charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Researchers are evaluating targeted therapeutic exercises for individuals with neurodegenerative diseases that affect walking. The study aims to improve how clinicians assess disease severity, apply exercise interventions that match the disease pathology, and measure the impact on balance and walking. The research focuses on conditions such as leukodystrophy, ataxia, LBSL, and adrenomyeloneuropathy among others. Participants will engage in an individually designed home exercise program focused on addressing walking impairments. This program will be remotely supervised to test the feasibility of such interventions and to optimize outcome measures that can be used in clinical monitoring and future trials. The exercise intervention will be tailored to each participant's condition and delivered in a home setting. During the study, participants will be assessed on changes in motor function and sleep quality using tools like the NeuroQOL lower extremity measure over a 12-week period. Researchers will monitor balance and walking improvements as well as the feasibility of remote supervision. The study includes healthy volunteers who can stand and walk for specific durations and involves ongoing clinical evaluations to ensure safety and measure progress. Total participation duration and follow-ups are designed to support these goals.

Krabbe disease is a rare condition affecting about 1 in 250,000 births, with most affected children having an early-infantile form that is often fatal if untreated. This study aims to build a global clinical database to better understand the symptoms that signal disease onset across different types of Krabbe disease. It also seeks to explore whether GALC enzyme levels or certain genetic mutations can predict how the disease progresses, and which neurodiagnostic tests may indicate disease onset or severity. Participants will provide detailed information through a questionnaire about their diagnosis, symptoms, genetic and enzyme activity data, and results from brain MRI and other neurological tests. Imaging data and physician reports, when available, will also be collected. Follow-up phone calls with parents or caregivers will gather updates on health status, disease progression, neurological symptoms, and developmental milestones. The collected data will be anonymized and stored in specialized databases to improve understanding and diagnosis of Krabbe disease. Throughout the study, researchers will analyze prognostic indicators including genetic and molecular markers, enzyme levels, and neurodiagnostic test results. The primary outcome measure is overall survival tracked for up to five years. The study involves ongoing data collection and monitoring to enhance diagnosis accuracy and support future therapy development for Krabbe disease.

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This research aims to better understand how these diseases develop over time and to analyze the effects of different interventions. The study is observational and focuses on disorders such as MLD, Krabbe Disease, ALD, and many other rare conditions affecting the nervous system. Participants are observed without receiving experimental treatments. The study collects data from patients who are receiving standard care, including those who have undergone Hematopoietic Stem Cell Transplantation (HSCT) and those receiving palliative care. Evaluations by a multidisciplinary team occur regularly: every 3 months during the first year, every 6 months in the second year, and once a year thereafter. During these visits, researchers assess key developmental areas including cognitive, language, gross and fine motor skills, and adaptive living skills over a 15-year period. Brain neurodegeneration is monitored using MRI diffusion tensor imaging in patients from birth to 5 years old, while exploratory biomarkers are also collected. This long-term follow-up helps track disease course and intervention outcomes for up to 15 years.

Researchers are studying leukodystrophies, inherited disorders affecting the brain's white matter, which impact about 1 in 7,500 children and have a high mortality rate over 30%. These conditions often cause serious complications like epilepsy, developmental decline, and intellectual disabilities. The study aims to improve diagnosis, care, and understanding of patient outcomes by collecting clinical histories and monitoring disease progression. This observational study is conducted through the Western Leukodystrophy Project at the University of Utah and Primary Children's Hospital, specialized centers for leukodystrophy care. Participants receive diagnosis support, treatment suggestions, and care guideline implementation. The study tracks patient health and disease evolution over time without testing new treatments. Participants are followed for up to 20 years, with yearly check-ins to monitor complications such as spasticity, respiratory and bulbar issues, hypotonia, cerebellar and language problems, and hospitalizations. Brain MRIs are done at enrollment and repeated approximately every five years. Clinical and diagnostic testing occurs at baseline and every three years. The study measures morbidity as the primary outcome, helping researchers understand long-term effects and responses to interventions like bone marrow transplant.

This research aims to explore the relationship between plasma sphingolipid levels and the effectiveness of radiotherapy in patients with primary liver cancer, specifically hepatocellular carcinoma. The study focuses on key metabolites like ceramide, sphingosine, and sphingosine-1-phosphate, which play roles in cell signaling and apoptosis. Researchers hypothesize that these sphingolipid levels may predict how well radiotherapy works, helping to improve treatment strategies for liver cancer. The study is a single-center, prospective observational project involving 260 patients undergoing radiotherapy for liver cancer. Plasma samples will be collected before, during, and after treatment to analyze sphingolipid metabolites using advanced mass spectrometry techniques. Patients will be grouped based on their response to radiotherapy, classified by imaging criteria into responders and non-responders. The study also monitors radiation-induced side effects such as liver disease, enteritis, and bone marrow suppression. Participants will be followed for up to four years after radiotherapy, with assessments at multiple time points including 1, 2, 6, 12, 18, 24, 36, and 48 months. Clinical imaging, laboratory tests, and adverse event monitoring will be performed to correlate sphingolipid levels with treatment outcomes and safety. The main outcome measure is the disease control rate assessed 12 weeks post-treatment, with additional measures including progression-free survival, overall survival, and treatment tolerability.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.